Not All [Sugar] Is Bad

It turn out that not all sugar is bad. Put another way, not everything in sugar is bad for diabetics. Sugar (sucrose) consists of one glucose and one fructose molecule, or 50% glucose and 50% fructose. The body does different things with glucose vs fructose.

There are several studies which tease out the differences between glucose and fructose. Here’s one of the studies (Kimber L. Stanhope, et.al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. The Journal of Clinical Investigation, 2009;5:119, pp 1322-1334). The study:

To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks.

Switching out between the two sugars sounds like a fairly easy test and should have resulted in identical results. And the results were the same for weight gain so both parts of sugar can make you fatter.

There was a very important difference, though, where the fat was located. In the group eating fructose the visceral adipose volume was significantly increased only in subjects consuming fructose. 

Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption.

In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption.

In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose.

These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

Interesting results. For a newer paper which summarized other studies on the subject see this (Stanhope KL, Schwarz J-M, Havel PJ. Adverse metabolic effects of dietary fructose: Results from recent epidemiological, clinical, and mechanistic studies. Current Opinion in Lipidology. 2013;24(3):198-206.)

More Evidence for Hyper-Insulinemia

An interesting study which adds some evidence to the Insulin-Obesity theory (Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, Greenberg AS, Roberts SB. A low glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial. Diabetes Care. 2005;28(12):2939–41.).

Two groups of people were put on two different diets. The two groups were matched and the diets were matched for calories. One of the diets was High Glycemic Index and the other was a Low Glycemic Index diet. The people who had higher fasting Insulin levels responded better to the Low Glycemic Index diet. The group with lower fasting Insulin levels responded to both diets in equal way.

The main finding from this pilot study was that healthy overweight women and men with relatively greater insulin secretion in response to a standard oral glucose tolerance test lost more weight when assigned to a low– glycemic load hypocaloric diet than to a high– glycemic load diet, but there was no differential effect of the two diets on weight loss in individuals who had relatively lower insulin secretion.

Saturated Fat and Liver Fat

There’s a study which indicates that PUFAs protect against accumulation of liver fat but SFA (saturated fatty acids) contribute to the accumulation of liver fat (Fredrik Rosqvist, David Iggman, Joel Kullberg, Jonathan Cedernaes, Hans-Erik Johansson, Anders Larsson, Lars Johansson, Håkan Ahlström, Peter Arner, Ingrid Dahlman, Ulf Risérus. Overfeeding Polyunsaturated and Saturated Fat Causes Distinct Effects on Liver and Visceral Fat Accumulation in Humans. Diabetes Jul 2014, 63 (7) 2356-2368). The study overfed young subject muffins for seven weeks made with PUFA or SFA. The SFA participants gained fat in their liver and the PUFA group did not gain liver fat.

However, there’s one interesting point in the study:

In the current study, a fructose–SFA interaction on liver fat is possible since the muffins contained significant amounts of fructose. Early animal data showed that carbohydrate-induced lipogenesis was inhibited by adding linoleic acid, whereas palmitate had no effect, and SFAs have enhanced steatosis and increased hepatic lipogenesis compared with PUFAs.

That makes a lot of sense. 

The PUFA was Sunflower Oil. The SFA was Palm Oil. It would have been interesting if the SFA was plant based.

Carbs, Not Saturated Fats, Increase Fat in Blood

Interesting study that gradually increased carbs and decreased fats shows that fats don’t increase fat in the blood, but carbs do (Volk BM, Kunces LJ, Freidenreich DJ, Kupchak BR, Saenz C, et al. (2014) Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome. PLOS ONE 9(11): e113605.).

Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced.

Blood Sugar and Fasting

A while back, I noticed that my Blood Sugar peaks around the second day of extended fasting. George Cahill did the seminal work measuring blood markers during starvation (Cahill, George. Fuel Metabolism in Starvation.). Here’s an interesting chart from that study that explains the sources of glucose during starvation.

This demonstrates the increase in blood sugar around day 2-3. Diabetics are particularly adept at GNG. Eventually though, even that reduces as the body becomes physiologically Insulin Resistant.

The chart can provide some idea of what happens in a ketogenic diet. Although someone on a ketogenic diet is eating enough food, their exogenous glucose is greatly reduced due to the low carbohydrate content of the diet. Glycogen stores lower next. When the glycogen stores get low the body then upregulates Glyconeogenesis (GNG).

This could also explain why when I see an increase in blood sugars on one morning I often see a drop in weight the following morning. The body is signalling that it is switching fuel to up-regulated GNG due to dropped Glycogen stores. Although these two sources are of the same magnitude in Cahill’s chart above they could well be less equally matched in a diabetic. It is possible that GNG in a diabetic outpaces the ability to pull from Glycogen stores.

 

The Carbohydrate-Insulin Model of Obesity

Here’s a very fresh study published in JAMA (David S. Ludwig, MD, PhD; Cara B. Ebbeling, PhD. The Carbohydrate-Insulin Model of Obesity: Beyond “Calories In, Calories Out”JAMA Intern Med. Published online July 2, 2018.). From the abstract:

According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high–glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure.

Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions.

Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance.

Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low fat diets.

Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity.

Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.

Here’s a good graphic from the paper:

Worth a read.

 

One of the Good Guys – Dr. Benjamin Bikman

I’ve spent too much time covering the keto hucksters (OK, mostly just Jimmy Moore but he’s a big enough target) so I thought I’d switch it up and look at one of the good guys – Dr. Benjamin Bikman (our YouTube playlist of Dr Bikman). I mentioned Ben in (Great BLOGs). He is a PhD who teaches at BYU and he’s got a lot to say about Protein over at his InsulinIQ site.

Here’s a video (High Intensity Health Episode 200) where he is interviewed.

Ben is one of the folks who came to nutrition from the exercise side. Ben really gets it about Insulin and obesity.

A video on Insulin and Glucagon.

 

The Big Fat Hack – Day 4

Jimmy Moore is doing a big fat hack. He’s on day 4. And Jimmy is producing more drama than ketones at this point.

Jimmy’s claim to have developed glucagon resistance is a curious one. Jimmy may have actually dropped his glycogen stores down to where there’s not enough glycogen to convert to glucagon when needed. Since Jimmy eats low protein he lacks protein as a substrate for GNG.

We know that Jimmy does everything possible to keep GNG from refilling his glycogen stores (other than stop eating fat). Does Low Carb PLUS Low Protein create a problem in refilling glycogen? This article has the clues (Glycogen Stores in Low Carb).

If that’s the case it really could be true that Jimmy’s low blood sugar isn’t met by glucagon. Equally, I don’t know how someone could differentiate between glucagon resistance and a lack of production of glucagon.

Jimmy’s ketones and blood sugar were:

Here’s Jimmy’s recovery strategy. Note the strategic placement of the F-Bomb products (one of the products Jimmy Moore promotes).

Looks like the big fat hack may have stopped his big fat hack.

Fasting and Gluconeogenesis

In my previous post (Low Carbs and Gluconeogenesis) I took a look at the low carb diet and Gluconeogenesis (GNG). The study found that GNG was increased by 14% in low carb diets. For folks who view GNG as the enemy that is challenging. After all, why go on a diet which makes your GNG even worse?

But, did you know that fasting increases GNG even more? This study looked at fasting and GNG (Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan. SC. 1996 Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest. 98:378–385.):

The contribution of gluconeogenesis to glucose production was 47+/-64% after 14 h, 67+/-64% after 22 h, and 93+/-62% after 42 h of fasting.

It would be wrong to think this means we should get up in the middle of the night to eat in order to prevent GNG. We should not fear GNG since it is necessary. Our bodies produce the amount of Glucose that our bodies need for those parts of the body which require Glucose. When we are on Low Carb diets we produce Glucose in response to demand.

A more interesting question is why GNG is overdriven in Type 2 Diabetics. This is the paper for that subject (Song S, Andrikopoulos S, Filippis C, Thorburn AW, Khan D, Proietto J. Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. Am J Physiol Endocrinol Metab. 2001 Aug;281(2):E275-82.).

The high-fat diet increased endogenous glucose production (21.9 +/- 4.4 vs. 32.2 +/- 4.8 micromol x kg(-1) x min(-1), P < 0.05) and alanine gluconeogenesis (4.5 +/- 0.9 vs. 9.6 +/- 1.9 micromol x kg(-1) x min(-1), P < 0.05).

Excess supply of dietary fat stimulates alanine gluconeogenesis via an increase in fructose-1,6-bisphosphatase protein levels

Looks like substrate availability can increase GNG – when the substrate is fat.

References